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Publication : SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue.

First Author  Shuai L Year  2019
Journal  Diabetes Volume  68
Issue  7 Pages  1449-1461
PubMed ID  31010955 Mgi Jnum  J:277362
Mgi Id  MGI:6315832 Doi  10.2337/db18-1103
Citation  Shuai L, et al. (2019) SIRT5 Regulates Brown Adipocyte Differentiation and Browning of Subcutaneous White Adipose Tissue. Diabetes 68(7):1449-1461
abstractText  The unique thermogenic capacity of brown adipocyte makes it an attractive target for antiobesity treatments. Several epigenetic regulators can control brown adipocyte development. In this study, we show that SIRT5, a member of the sirtuins, is required for brown adipocyte differentiation and essential for brown adipogenic gene activation in vitro. Furthermore, we find out that knockdown of SIRT5 reduces intracellular alpha-ketoglutarate concentration, which leads to elevated H3K9me2 and H3K9me3 levels at promoter regions of Ppargamma and Prdm16 loci. Finally, we discover that SIRT5 knockout mice on the Sv129 background exhibit less browning capacity in subcutaneous white adipose tissue compared with controls and show apparent cold intolerance, suggesting that SIRT5 can modulate the browning process in vivo. Thus, our study uncovers a new biological function of SIRT5 in brown adipocyte differentiation and a mechanism by which SIRT5 regulates brown adipogenic gene activation at least partly through an indirect effect on histone modifications. Our study extends the linkage between epigenetics and cell differentiation.
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